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Biomedical subjects

G Bianchetti

Publications and source records attributed to G Bianchetti.

At least 55 records · Page 3Linked to original sources
PubMed1984

Betaxolol kinetics in hypertensive children with normal and abnormal renal function.

The kinetic and clinical profile of betaxolol--a beta 1-selective blocker with 80% to 90% bioavailability and a 16 to 20 hr t1/2--were studied in ten children aged 5 to 13 yr with chronic renal hypertension and mild to severe renal failure. An IV dose of 20 mg of betaxolol per 1.73 m2 body surface area (BSA) was followed by six daily oral doses. Six patients were maintained on combination therapy and four on betaxolol alone; two of these were newly treated. After the intravenous dose, t1/2 (mean +/- SE) was 19.9 +/- 1.7 hr, total clearance 0.30 +/- 0.03 l/kg/hr, and volume of distribution 8.2 +/- 0.7 l/kg. Clearance adjusted for BSA was 7.9 +/- 0.6 l/hr. The t1/2 correlated linearly to serum creatinine levels. After the last dose, peak concentration was 97.4 +/- 7.6 ng/ml, and t1/2 19.4 +/- 2.7 hr. Betaxolol 24-hr blood levels were twice as high as after the first dose. Blood pressure was reduced in two newly treated patients and two patients on combination therapy; previous responses were maintained in the others. The maximum effect was reached after the first dose and was maintained throughout the study week. Our results indicate that betaxolol disposition in children aged 5 to 13 yr with different degrees of renal failure is of the same order as that in young healthy adults, implying that there may be a higher rate of non-renal clearance. Renal failure-induced modification led to a doubling of the t1/2 in the most severe cases, again as in adult renal patients. There is an antihypertensive effect.

Acute Kidney Injury↗
PubMed1983

Enhanced effect of haloperidol and apomorphine after hypophysectomy: pharmacokinetic considerations.

The behavioural effects of both apomorphine (stereotypies) and haloperidol (catalepsy and reversal of stereotypies) were significantly enhanced in hypophysectomized rats compared with sham-operated rats. Both the efficacy and duration of action were increased Hypophysectomized animals had significantly greater brain haloperidol concentrations than did sham-operated animals. The data suggest that changes in brain drug concentrations following hypophysectomy at least partially explain the behavioural alterations seen in this test situation.

Animals↗
PubMed1983

Therapeutic drug monitoring of psychotropic drugs in children.

In several areas of medicine, therapeutic drug monitoring (TDM) has been proven to be a very useful tool for optimizing the therapeutic potential of various drugs and for minimizing the risk of adverse events. In pediatrics the value of TDM is generally accepted for drugs such as Theophylline and/or antiepileptics, but it is still strongly questioned for classes of drugs such as neuroleptic and tricyclic antidepressants. However, in the last 5 years evidence has been produced indicating that TDM may be a very useful tool in pediatric neuropsychiatry too. In fact, if on the one side therapeutic windows have been defined for major neuroleptics and tricyclic antidepressants, on the other side clear relationships between drug plasma concentrations and the incidence and severity of adverse reactions have been reported. Data derived from our own experience of 5 years of TDM in pediatric neuropsychiatry will be described together with data from the literature. It appears that at least for four major drugs, Haloperidol, Chlorpromazine, Imipramine, and Chlorimipramine, drug plasma levels monitoring during chronic treatment does help in a significant manner in optimizing the treatment.

Adolescent↗
PubMed1982

[Plasma level monitoring of psychotropic drugs in children. I-Haloperidol (author's transl)].

Monitoring of haloperidol plasma levels during long-term treatment is not commonly practised in adults and even less in children. In this study, haloperidol plasma levels were measured in children and teenagers with psychotic episodes or abnormal movements. Steady state concentrations ranged from 0.7 to 19 ng/ml. They were apparently unrelated to the doses administered (15-285 micrograms/kg/day), and variations of up to 15-fold were observed with the same dosage. In contrast, a significant correlation (p less than 0.02) was determined between age and dose-concentration ratio. Side-effects also seemed to be significantly related to plasma levels (p less than 0.01); they occurred at concentration higher than 6 ng/ml. Therapeutic response was observed with plasma concentrations of 1 to 4 ng/ml in cases with abnormal movements, but no dose-effect relationship was found in patients with psychotic episodes.

Adolescent↗
PubMed1982

High doses of haloperidol in schizophrenia. A clinical, biochemical, and pharmacokinetic study.

The effects of high doses of haloperidol on clinical status and plasma neuroleptic and prolactin concentrations and CSF levels of homovanillic acid (HVA) and gamma-aminobutyric acid (GABA) were investigated in three paranoid schizophrenic patients over six weeks. The patients had been receiving haloperidol. Oral dosages were increased at weekly intervals from 10 to 200 mg/day and then reduced to 10 mg/day. The increase did not affect paranoid symptoms. Neurological side effects were slightly increased in two patients and moderately reduced in one. Plasma prolactin levels, initially high, increased when the dosage was increased to 100 mg/day but did not increase further. The CSF levels of HVA and GABA increased to day 7 but returned to initial values on day 28 in two patients; they were decreased to day 28 in one patient.

Adult↗
PubMed1982

Haloperidol plasma level monitoring in neuropsychiatric patients.

The available data on haloperidol pharmacokinetics and haloperidol plasma level monitoring in neuropsychiatric patients are reviewed and compared with authors' personal observations. It appears that although haloperidol disposition can be described by linear kinetics in volunteers, this is not the case in patients in whom a 7--10-fold variability in plasma levels is observed for the same dosage together with the possibility of saturation kinetics and/or first pass effect. Anticholinergics may interfere with haloperidol absorption, and significant differences in disposition rate and binding have been observed in children and cirrhotic patients. A clear correlation appears to exist between plasma concentrations and side effects or adverse reactions with threshold levels for extrapyramidal syndromes of 6--9 ng/ml. Threshold levels for therapeutic effects vary with syndromes and age. In Gilles de la Tourette syndrome, active levels are of the order of 1--3 ng/ml, whereas in psychotic syndromes levels of 10--15 ng/ml are requested. In mania, a good therapeutic effect has been observed with plasma levels of 2.5--4.5 ng/ml. In general, children require lower plasma levels for the same therapeutic effects. In chronic unresponsive schizophrenic patients, poor drug bioavailability is not the major factor for the lack of response, and the possibility that these patients constitute a nosological subgroup is suggested. Therapeutic drug monitoring of haloperidol appears justified because (a) no direct relationship exists between daily doses and haloperidol steady-state plasma levels; (b) there is a possibility of saturation kinetics at higher doses; (c) commonly associated drugs or diseases may alter the kinetic profile of the drug; (d) drug disposition is faster in children than in adults; (e) optimal plasma concentration appears to differ in various pathological syndromes and age groups; and (f) side-effects and adverse reactions are clearly related to haloperidol plasma levels.

Chronic Disease↗
PubMed1982

[Use of haloperidol in high doses in schizophrenia. Clinical, biochemical and pharmacokinetic study].

The effect of high doses of haloperidol on the clinical status, plasma neuroleptic and prolactin concentrations as well as on CSF HVA and GABA levels was investigated in 3 paranoid schizophrenic patients over a 6 weeks period. When the study was initiated patients had been on haloperidol (10 mg a day) for 4-10 weeks. Oral doses were increased at weekly intervals from 10 (day 0) to 100 (day 7) and 200 (days 14 to 28) mg a day and then reduced to 100 (day 35) and 10 (day 42) mg/day. A linear relationship was observed between plasmatic levels and daily doses of haloperidol. In neither patient, the increase in haloperidol dosage affected paranoid symptoms. Neurological side effects were slightly increased in 2 cases and moderately reduced in one case. Prolactin plasma levels, already high at the onset of the study rose when increasing the dose to 100 mg a day but did not increase further despite increment in the haloperidol dosage. CSF levels of HVA and GABA rose from day 0 to day 7 but were back to the initial values on day 28 in 2 patients and were decreased from day 0 to day 28 in one patient. For the 3 patients a close correlation was observed between changes in CSF HVA and GABA levels. It is concluded that high doses of haloperidol, although causing biochemical changes compatible with the occurrence of dopamine target cell supersensitivity, do not lead to any clinical improvement in the 3 studied schizophrenic patients.

Adult↗
PubMed1981

Determination of vincamine in human plasma using automated high-performance liquid chromatography.

A specific and sensitive high-performance liquid chromatographic method for the quantitative determination of vincamine at therapeutic concentrations in plasma is described. The column was packed with Spherisorb ODS 5 micrometer, and the mobile phase was acetonitrile-potassium phosphate (0.02 M, pH 2.3) (50:50) with a flow-rate of 10 ml/min. Detection was at 230 nm. Using automated large-volume injection of a non-eluting solvent (0.02 M potassium phosphate) the method was capable of the analysis of a large number of samples daily. The coefficient of variation of the procedure was 4.8% at a plasma vincamine concentration of 10 ng/ml

Chromatography, High Pressure Liquid↗
PubMed1980

Beta-adrenoceptor blocking effects and pharmacokinetics of betaxolol (SL 75212) in man.

1 The pharmacological effects and the pharmacokinetics of betaxolol (SL 75212), a new beta-adrenoceptor blocking agent, were compared with those of propranolol and a placebo in a double-blind trial involving six healthy volunteers. 2 Heart rate (HR), myocardial contractile force (MCF), systolic blood pressure (SBP) and peak expiratory flow rate (PEFR) were measured at rest and during vigorous exercise before and at intervals up to 25 h after oral administration of the drugs. In addition, plasma renin activity (PRA) at rest and blood levels of betaxolol and propranolol were determined. 3. Betaxolol proved to be a potent and long-lasting beta-adrenoceptor blocking drug, devoid of intrinsic beta-sympathomimetic activity. Its beta-adrenoceptor blocking action was shown to four-fold that of propranolol at the cardiac and renal levels and to last at least 25 h after drug intake. 4 The peak blood level of betaxolol was reached 2 to 4 hr after its administration, the first-pass loss is likely to be low and the half-life is 12.3 h. These pharmacokinetic data are perfectly consistent with the long duration of the pharmacological effects of betaxolol in man.

Adrenergic beta-Antagonists↗
PubMed1980

Cardiovascular effects of single oral doses of the new beta-adrenoceptor blocking agents betaxolol (SL 75212) in healthy volunteers.

1 The effects of betaxolol (SL 75212), a new beta-adrenoceptor blocking agent, on the cardiovascular response to exercise have been studied in six normal subjects after placebo and single oral doses of 5, 10, 20 and 40 mg given double-blind in a randomized sequence. 2 All doses reduced exercise heart rate, with a significant reduction persisting to 23 h after doses of 20 mg and 40 mg. Systolic blood pressure on exercise was reduced after all doses, with a reduction continuing to 23 h after doses of 10 mg and above. 3 The mean elimination half-life of SL 75212 was 17.5 +/- 3.9 h. The plasma clearance ranged from 0.15--0.48 1 kg-1 h-1 and the volume of distribution from 5.8--13 1 kg-1. 4 There was a significant correlation between the peak blood levels and change in exercise heart rate (r = 0.53, P less than 0.05) and between the area under the blood concentration curve and the effect of the exercise heart rate (r = 0.55, P less than 0.01).

Adrenergic beta-Antagonists↗
PubMed1980

Blood concentrations and pharmacodynamic effects of betaxolol (SL 75212) a new beta-adrenoceptor antagonist after oral and intravenous administration.

1 In normal subjects, intravenous betaxolol given in doses which inhibited the tachycardia of exercise failed to affect the peak expiratory flow rate. 2 From 2 to 48 h after administration of 150 micrograms/kg in four normal subjects, there was no significant difference between the blood levels, whether given orally or intravenously. 3 At all times, heart rate and blood pressure, at rest and during exercise, were reduced equally after administration by both routes, but the area under the curve of exercise heart rate against time was significantly smaller (P < 0.05) after intravenous drug. 4 The absolute bioavailability of betaxolol was 89 +/- 5%.

Administration, Oral↗
PubMed1980

Pharmacokinetics of the new beta-adrenoceptor blocking agent betaxolol (SL 75212) in man after repeated oral administration.

(+/-)-1-(Isopropylamino)-3-[p-(2-cyclopropyl-methoxyethyl)-phenoxy]-2-propanol HCl (betaxolol, SL 75212) was given to groups of healthy volunteers, 10 mg daily for 7 days followed by 20 mg daily 7 days in one group, and increasing daily doses up to 60 mg/day for a total of 15 days in the other group. The pharmacokinetics were studied during dosing and in the washout period. The pharmacokinetic characteristics were unchanged after repeated doses, T/2 16-22 h, Vd 7.7-8.8 l/kg; clearance 0.28-0.33 l/h/kg.

Administration, Oral↗